Switching of the nonallelic forms of fetal hemoglobin during late gestation

The gamma chains of human fetal hemoglobin occur in two nonallelic forms, designated G gamma and A gamma, which differ from one another in having either glycine or alanine as their 136th residue respectively. In newborns, G gamma comprises about 75% of the total gamma chains, while in adults, G gamma comprises about 40% of the total gamma chains. The timing of the switching events that lead to the alteration of the rates of production of G gamma and A gamma are still unknown. Umbilical cord red blood cells from term infants were separated by density gradient fractionation into four age-dependent fractions. Red blood cell size and reticulocyte content decreased and the percent fetal hemoglobin increased with increasing gradient densities, confirming age-dependent density separation. The percent G gamma was determined by two methods on fractionated cord red blood cells to determine if the switch in the production ratio of the nonallelic forms of gamma chains began during late gestation. The G gamma content of fetal hemoglobin was found to decrease with decreasing red blood cell age, demonstrating that the switch from predominately glycine-containing gamma chains to predominately alanine-containing gamma chains begins during late gestation.